Reactions 1305 - 12 Jun 2010

ADR news from ISPORAtlanta, Georgia, US May 2010

The following report highlights a number of studies Aliskiren renal risks highlightedpresented at the 15th Annual International Meeting of Treatment with aliskiren may be associated withthe International Society for Pharmacoeconomics and angioedema and renal dysfunction, and should not beOutcomes Research (ISPOR) that considered adverse taken by patients with risk factors for renal dysfunction,drug reactions (ADRs) and associated issues. according to postmarketing safety data.4

Adverse symptom reporting is crucial in clinical trials US FDA Adverse Event Reporting System data wereand drug labelling to assess and ensure patient safety. retrospectively analysed for the period JanuaryThe Common Terminology Criteria for Adverse Events 2007–December 2008. Compared with other renin-(CTCAE) is the standard approach used to collect angiotensin-aldosterone system modulators, aliskirenadverse symptoms data in cancer trials. Researchers was associated with the highest ARR for angioedemafrom the US conducted a retrospective analysis of (EBGM** 3.9; 95% CI 3.2, 4.7), renal dysfunction (3.4;medical charts to evaluate the reliability of this 2.6, 4.5), dry cough (11.0; 7.8, 14.2) and diarrhoea (4.3;information collection in a sample of 433 patients at 3.2, 5.8). The study’s author says that, while longitudinalMemorial Sloan-Kettering Cancer Center.1 studies and clinical awareness are warranted,

"regulatory changes in product label and safetyAdverse symptom reporting questionablecommunications, e.g. dear-health care-professionalPatients were evaluated via CTCAE items by a clinicianletters are recommended".in an office suite, and again shortly afterwards by a

second clinician in a chemotherapy suite, with no Atypical antipsychotics not linked topassage of information between clinicians; the average fractures . . .time between evaluations was 70.42 minutes. A team of investigators based in the US performed aFor the first postchemotherapy visit, intraclass retrospective cohort analysis to examine the risk of falls/correlation coefficients were moderate for fatigue fractures associated with atypical versus typical(0.52), dyspnoea (0.75), diarrhoea (0.63), constipation antipsychotic used in community-dwelling older adults.5(0.48), nausea (0.55), vomiting (0.50) and neuropathy They identified 11 160 adults (aged ≥ 50 years) as new(0.73). These values remained stable over ≤ 6 users of either atypical (n = 5580) or typicalsubsequent visits, and did not differ based on gender, antipsychotics. Within 1 year’s follow-up, falls/femurage or time lapsed between evaluations. fractures occurred among 456 atypical antipsychoticThe researchers say that this "lower than expected" recipients (8.06%) and 375 typical antipsychoticlevel of agreement between different clinicians recipients (6.72%) – a nonsignificant difference.reflects "limited reliability of clinical reporting" of However, duration of atypical or typical antipsychoticinformation. They contend that this finding has therapy of > 90 days was significant associated with animplications for clinical trials as it "brings into question increased risk of falls/fracture, compared withthe reliability or accuracy of symptom safety < 30 days’ therapy.information".

. . . but use could lead to urinaryLess neuropathy with docetaxel vs paclitaxel incontinenceDocetaxel-based adjuvant treatment is associated Use of atypical antipsychotics leads to an increasedwith less neuropathy than paclitaxel in breast cancer risk of urinary incontinence in elderly nursing homepatients, reports a group of researchers from the US.2 In residents, shows a study based on 2004 US Nationaltheir retrospective study* conducted among 3619 Nursing Home Survey data.6patients, a significantly lower frequency of neuropathy A total of 8722 residents used psychotropicwas observed in the follow-up period for docetaxel- medications, of whom 2366 (27.2%) usedbased versus paclitaxel-based treatments (7.0% vs antipsychotics and 5005 (57.58%) were incontinent.10.6% of patients). Similar differences were noted when Regression analysis of these data revealed that residentspatients were stratified by dosing intervals, and after receiving atypical antipsychotics had an 81.5%adjusting for covariates. increased risk of being incontinent (p < 0.0001),Another US study* also found that docetaxel was compared with those on other psychotropicassociated with a lower risk of severe neuropathy and medications. The presence of comorbidities enhancedchemotherapy interruption than paclitaxel.3 The Georgia the urinary incontinence risk by 58.9% (p < 0.0001);Cancer Specialist Database (2003–2008) was used, residents who used bedrails, chairs or truncal restraintssupplemented with chart abstraction, to assess adverse also had higher risks of being incontinent.outcomes among patients with stage I–III breast cancerreceiving adjuvant therapy with either docetaxel Promethazine, ondansetron AEs common(n = 591) or paclitaxel (338). Univariate analysis Adverse events (AEs) related to promethazine andshowed that paclitaxel was associated with higher ondansetron use among children and women ofrates of severe neuropathy and use of neuropathy- childbearing age are common, say researchers from therelated medications than docetaxel (4.9% vs 1.0% and US.7

28.1% vs 7.6%, respectively) within 6 months. In Their retrospective analysis utilised data from the USaddition, chemotherapy treatments were significantly FDA’s Adverse Events Reporting System Database formore likely to be affected among paclitaxel than the period 1997–2006. A total of 392 229 AEs amongdocetaxel recipients (7.1% vs 1.5%). Adjusted analysis infants and children aged 0–6 years and women agedconfirmed these results in favour of docetaxel. 15–50 years were reported for promethazine and

282 056 for ondansetron.Among women, the most frequent AE pregnancy

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Reactions 12 Jun 2010 No. 13050114-9954/10/1305-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved

Single Article

BREAST CANCER PATIENTS - RESULTS FROM A US COMMUNITYoutcomes were maternal complications (26%),ONCOLOGY CENTER. 15th Annual International Meeting of the Internationalpremature labour (9%), maternal drugs affecting foetus Society for Pharmacoeconomics and Outcomes Research : abstr. PCN13, 15May 2010. Available from: URL: http://www.ispor.org.(8%) and spontaneous abortion (4%). The most

4. Ali AK. POSTMARKETING SAFETY EVALUATION OF ALISKIRENfrequently occurring AEs among infants and childrenHEMIFUMARATE, A NEW MOLECULAR ENTITY. 15th Annual

were neonatal respiratory arrest (0.25%) and neonatal International Meeting of the International Society for Pharmacoeconomics andOutcomes Research : abstr. PCV2, 15 May 2010. Available from: URL: http://apnoeic attack (0.17%). Off-label and long-term use ofwww.ispor.org.promethazine and ondansetron for nausea and 5. Mehta S, et al. RISK OF FALLS AND FRACTURES IN OLDER ADULTS

vomiting during pregnancy "should be USING ATIPSYCHOTIC AGENTS - A PROPENSITY-MATCHEDRETROSPECTIVE COHORT STUDY. 15th Annual International Meeting ofrecommended with cautions", comment thethe International Society for Pharmacoeconomics and Outcomes Research :researchers. abstr. RM3, 15 May 2010. Available from: URL: http://www.ispor.org.

6. Khokhawalla I, et al. EFFECT OF ATYPICAL ANTIPSYCHOTICS ON* supported by sanofi-aventis URINARY INCONTINENCE IN US NURSING HOME RESIDENTS USINGPSYCHOTROPIC MEDICATIONS. 15th Annual International Meeting of the** Empiric Bayes Geometric MeanInternational Society for Pharmacoeconomics and Outcomes Research : abstr.

1. Atkinson TM, et al. RELIABILITY OF CLINICIAN VS. CLINICIAN PUK4, 15 May 2010. Available from: URL: http://www.ispor.org.ADVERSE SYMPTOM REPORTING. 15th Annual International Meeting of 7. Seddoh SA, et al. ADVERSE EVENTS OF PROMETHAZINE ANDthe International Society for Pharmacoeconomics and Outcomes Research : ONDANSETRON IN YOUNG CHILDREN AND WOMEN OF CHILD-abstr. PCN3, 15 May 2010. Available from: URL: http://www.ispor.org. BEARING AGE: A PHARMACOVIGILANCE STUDY BASED ON THE

2. Burke JP, et al. ASSESSMENT OF NEUROPATHY IN CLAIMS DATA AND FDA ADVERSE EVENT REPORTING SYSTEM. 15th Annual InternationalTHE ASSOCIATION WITH DOCETAXEL (DC) AND PACLITAXEL (PC) IN Meeting of the International Society for Pharmacoeconomics and OutcomesADJUVANT BREAST CANCER (BC). 15th Annual International Meeting of Research : abstr. PGI2, 15 May 2010. Available from: URL: http://the International Society for Pharmacoeconomics and Outcomes Research : www.ispor.org.abstr. PCN5, 15 May 2010. Available from: URL: http://www.ispor.org. 801140561

3. Zhao L, et al. TAXANE USE AND NEUROPATHY IN EARLY STAGE

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0114-9954/10/1305-0002/$14.95 © 2010 Adis Data Information BV. All rights reservedReactions 12 Jun 2010 No. 1305